1. Field of the Invention
The present invention relates to the storage agent for preservation of an animal cell or organ and preserved process, particularly the storage agent applied for animal cells, transplant internal organs, blood, corpuscle or blood platelet, stabilizer of protein and the storage agent prevented, treated and improved organ injury caused on an organ transplant operation.
2. Description of the Related Art
Ordinary method of cell storage is employed preserving method by freezing at extra low temperature of −196° C. and original cell is gotten by rapid thawing of frozen cell as needs arises. However, the survival ratios of cells after thawing and fusion is low, depending on a kind of cells and examiner's skill, while those of normal and useful cells such as Langerhans islets and liver cells except cancer cell is about 10 to 30%.
Moreover, in case of bloods, corpuscle or blood platelet, the period of validity is a very short time of 12 to 72 hours because of impossibly preserving by freezing. Inspite of a fact that transplanting an internal organ recently increases, preserving method for transplanted organ still confront researcher as serious theme. These problems are greatly related to cell damage and tissue injury.
As a result of a progress in surgical operation and immunosuppressive agent, case of transplanting an internal organ recently increases. In ideal transplanting, the internal organ removed from the donor is immediately transplanted to the recipient, but in many cases, transplanted operations do not immediately happen to occur. It is very important to preserve precious organ for transplantation because the operation is very urgent. There are two kinds of preservation methods for internal organ, in which preservation method at low temperature is intended to reduce metabolism on one hand, while perfusion preservation method is intended to maintain metabolism on the other hand. Many kinds of storage agents are developed in order to apply for these methods and clinically undergone.
Euro-Collin's solution was employed in early stage of transplantation, having validity period of less than 24 hours in liver case and expected to make prolong the validity period. Recently, UW solution was developed by Group of University of Wisconsin (University of Wisconsin, Wahlberg, J. A. et al, Transplantation, 43, pp.5-8, 1987) and applied for storage agent of pancreatic transplantation. This solution is useful for storage agents of not only pancreatic but also liver and kidney transplantation and the validity period of liver has possibly prolonged to 24 hours.
However, even these solutions can not be satisfied still, so new solution is expected to develop and invent in order to preserve viability and effectiveness of internal organs for a long time.
Generally speaking of all kinds of internal organs, functional injury of transplanted organ is inflicted based on a reason why free radicals generated at ischomia or resuming blood flow cause to prompt lipid peroxidation of biological membrane. Therefore, if cell injury caused on generation of lipid peroxidation, can be prevented, it is possible to develop novel effective storage agent.
These problems are greatly related to proliferation and division of the cells. Therefore, it seems to be big possibility of the accomplishing objective if proliferation and division of the cells can be freely controlled. The injury of cells or organs largely relates to active oxygen (O−2 ) yielded when hypoxanthin converted from adenosine tri-phosphate (ATP) in cell mitochondria changes to xanthine. Most serious problem come from the injuries, is carcinogenesis phenomenon, in which the cancer formation seems to be composed of two stages of carcinogenesis initiation and promotion. In carcinogenesis initiation stage, several kinds of carcinogenic substances inflict the cell DNA, mutation happens to occur, and normal organs become cancerous by infinite amplification of the cell. The active oxygen affects on the mutation and causes to aging and various plagues by super peroxide generated from the oxygen.
Recently, there are many reports concerning free radical effectiveness on living organ and mechanism of anti-oxidizing agent. As well known anti-oxidizing agents, super oxide dimustarse (SOD) is pointed out as enzyme type, while vitamin E and C, glutathione, carotinoid, flavonoid, saccharide, chelate of iron, uric acid, and albumin are pointed out as non-enzyme type.
There are no reports with respect to proliferation control of cells and preservation of tissue and internal organ. However, it is recently reported that green tea polyphenol shows effects of anti-oxidizing, deodorization action, antibacterial and anticancer effect, and is fabricated cheap and large quantities as material of functional foods.